Probing the Role of a Regional Quantitative Assessment of Amyloid PET

2021 ◽  
pp. 1-14
Author(s):  
Enrico Peira ◽  
Matteo Grazzini ◽  
Mateo Bauckneht ◽  
Francesco Sensi ◽  
Paolo Bosco ◽  
...  
Keyword(s):  
Neuropsychological Assessment ◽  
Verbal Fluency ◽  
Verbal Learning ◽  
Regional Distribution ◽  
Amyloid Β ◽  
Standardized Uptake Value ◽  
Brain Regions ◽  
Amyloid Pet ◽  
Semantic Verbal Fluency

Background: In clinical practice, the amy-PET is globally inspected to provide a binary outcome, but the role of a regional assessment has not been fully investigated yet. Objective: To deepen the role of regional amyloid burden and its implication on clinical-neuropsychological features. Materials: Amy-PET and a complete neuropsychological assessment (Trail Making Test, Rey Auditory Verbal Learning Test, semantic verbal fluency, symbol digit, Stroop, visuoconstruction) were available in 109 patients with clinical suspicion of Alzheimer’s disease. By averaging the standardized uptake value ratio and ELBA, a regional quantification was calculated for each scan. Patients were grouped according to their overall amyloid load: correlation maps, based on regional quantification, were calculated and compared. A regression analysis between neuropsychological assessment and the regional amyloid-β (Aβ) load was carried out. Results: Significant differences were observed between the correlation maps of patients at increasing levels of Aβ and the overall dataset. The Aβ uptake of the subcortical gray matter resulted not related to other brain regions independently of the global Aβ level. A significant association of semantic verbal fluency was observed with ratios of cortical and subcortical distribution of Aβ which represent a coarse measure of differences in regional distribution of Aβ. Conclusion: Our observations confirmed the different susceptibility to Aβ accumulation among brain regions. The association between cognition and Aβ distribution deserves further investigations: it is possibly due to a direct local effect or it represents a proxy marker of a more aggressive disease subtype. Regional Aβ assessment represents an available resource on amy-PET scan with possibly clinical and prognostic implications.

scholarly journals Cross-sectional associations of tau-PET signal with cognition in cognitively unimpaired adults

Neurology ◽  
2019 ◽  
Vol 93 (1) ◽  
pp. e29-e39 ◽  
Author(s):  
Val J. Lowe ◽  
Tyler J. Bruinsma ◽  
Heather J. Wiste ◽  
Hoon-Ki Min ◽  
Stephen D. Weigand ◽  
...  
Keyword(s):  
Entorhinal Cortex ◽  
Medial Temporal Lobe ◽  
Memory Performance ◽  
Standardized Uptake Value ◽  
Brain Regions ◽  
Population Based ◽  
Cognitive Test ◽  
Amyloid Pet ◽  
Cross Sectional ◽  
Tau Pet

ObjectiveTo assess cross-sectional associations of neurofibrillary tangles, measured by tau-PET, with cognitive performance in cognitively unimpaired (CU) adults.MethodsTau- and amyloid-PET were performed in 579 CU participants aged 50–98 from the population-based Mayo Clinic Study of Aging. Associations between tau-PET signal in 43 brain regions and cognitive test scores were assessed using penalized linear regression. In additional models, participants were classified by normal/abnormal global amyloid-PET (A+/A−) and normal/abnormal regional tau-PET (T+/T−). Regional tau-PET cutpoints were defined as standardized uptake value ratio (SUVR) greater than the 95th percentile of tau-PET SUVR in that region among 117 CU participants aged 30–49.ResultsHigher tau-PET signal was associated with poorer memory performance in all medial temporal lobe (MTL) regions and also in the middle temporal pole and frontal olfactory regions. The largest association with tau-PET and memory z scores was seen in the entorhinal cortex; this association was independent of tau-PET signal in other brain regions. Tau-PET in the entorhinal cortex was also associated with poorer global and language performance. In the entorhinal cortex, T+ was associated with lower memory performance among both A− and A+.ConclusionsTau deposition in MTL regions, as reflected by tau-PET signal, was associated with poorer performance on memory tests in CU participants. The association with entorhinal cortex tau-PET was independent of tau-PET signal in other brain regions. Longitudinal studies are needed to understand the fate of CU participants with elevated medial temporal tau-PET signal.

The role of MMP genes in recurrent depressive disorders and cognitive functions

2016 ◽  
Vol 28 (4) ◽  
pp. 221-231 ◽  
Author(s):  
Kinga Bobińska ◽  
Janusz Szemraj ◽  
Piotr Gałecki ◽  
Monika Talarowska
Keyword(s):  
Gene Expression ◽  
Cognitive Functions ◽  
Protein Level ◽  
Verbal Fluency ◽  
Verbal Learning ◽  
Rna Extraction ◽  
Human Organism ◽  
Enzyme Linked Immunosorbent Assay ◽  
Separate Analysis

ObjectiveAmong the 28 metalloproteinases described so far, 23 can be found in the human organism, but only few are expressed in the human brain. The main objective of this study was to analyse the relationship between MMP-2, MMP-9 and TIMP-2 gene expression and cognitive performance.MethodsThe study comprised 234 subjects: patients suffering from recurrent depressive disorder (rDD, n=139) and healthy subjects (HS, n=95). The cognitive function assessment was carried out with the help of the following tests: Trail Making Test, The Stroop Test, Verbal Fluency Test and Auditory Verbal Learning Test. Gene expression on the mRNA and protein level was evaluated for MMP-2, MMP-9 and TIMP-2 in both groups using RNA extraction, reverse transcription and enzyme-linked immunosorbent assay.ResultsBoth mRNA and protein expression levels of all the genes were significantly lower in rDD subjects as compared with HS. Having analysed the entire experimental group (N=234), significant interrelations were found between the expression of the analysed genes and the results of the tests used to measure cognitive functions. Increased expression on both the mRNA and the protein level was associated in each case with better performance of all the tests conducted. After carrying out a separate analysis on the people from the rDD group and the HS group, similar dependencies were still observed.ConclusionsThe results of our study show decreased expression of MMP-2, MMP-9 and TIMP-2 genes on both mRNA and protein levels in depression. Elevated expression of MMP-2, MMP-9, TIMP-2 positively affects cognitive efficiency: working memory, executive functions, attention functions, direct and delayed auditory–verbal memory, the effectiveness of learning processes and verbal fluency. The study highlights the important role of peripheral matrix metalloproteinases genes in depression and cognitive functions.

scholarly journals Post-mortem analyses of PiB and flutemetamol in diffuse and cored amyloid-β plaques in Alzheimer’s disease

2020 ◽  
Vol 140 (4) ◽  
pp. 463-476
Author(s):  
Milos D. Ikonomovic ◽  
Christopher J. Buckley ◽  
Eric E. Abrahamson ◽  
Julia K. Kofler ◽  
Chester A. Mathis ◽  
...  
Keyword(s):  
Frontal Cortex ◽  
Three Dimensional ◽  
Amyloid Β ◽  
Brain Regions ◽  
Area Coverage ◽  
Amyloid Pet ◽  
Tissue Sections ◽  
Total Fluorescence ◽  
Percent Area ◽  
Diffuse Plaques

Abstract Specificity and sensitivity of positron emission tomography (PET) radiopharmaceuticals targeting fibrillar amyloid-β (Aβ) deposits is high for detection of neuritic Aβ plaques, a mature form of Aβ deposits which often have dense Aβ core (i.e., cored plaques). However, imaging-to-autopsy validation studies of amyloid PET radioligands have identified several false positive cases all of which had mainly diffuse Aβ plaques (i.e., plaques without neuritic pathology or dense amyloid core), and high amyloid PET signal was reported in the striatum where diffuse plaques predominate in Alzheimer’s disease (AD). Relative contributions of different plaque types to amyloid PET signal is unclear, particularly in neocortical areas where they are intermixed in AD. In vitro binding assay and autoradiography were performed using [3H]flutemetamol and [3H]Pittsburgh Compound-B (PiB) in frozen brain homogenates from 30 autopsy cases including sporadic AD and non-AD controls with a range of brain Aβ burden and plaque density. Fixed tissue sections of frontal cortex and caudate from 10 of the AD cases were processed for microscopy using fluorescent derivatives of flutemetamol (cyano-flutemetamol) and PiB (cyano-PiB) and compared to Aβ immunohistochemistry and pan-amyloid (X-34) histology. Using epifluorescence microscopy, percent area coverage and fluorescence output values of cyano-PiB- and cyano-flutemetamol-labeled plaques in two-dimensional microscopic fields were then calculated and combined to obtain integrated density measurements. Using confocal microscopy, we analysed total fluorescence output of the entire three-dimensional volume of individual cored plaques and diffuse plaques labeled with cyano-flutemetamol or cyano-PiB. [3H]Flutemetamol and [3H]PiB binding values in tissue homogenates correlated strongly and their binding pattern in tissue sections, as seen on autoradiograms, overlapped the pattern of Aβ-immunoreactive plaques on directly adjacent sections. Cyano-flutemetamol and cyano-PiB fluorescence was prominent in cored plaques and less so in diffuse plaques. Across brain regions and cases, percent area coverage of cyano-flutemetamol-labeled plaques correlated strongly with cyano-PiB-labeled and Aβ-immunoreactive plaques. For both ligands, plaque burden, calculated as percent area coverage of all Aβ plaque types, was similar in frontal cortex and caudate regions, while integrated density values were significantly greater in frontal cortex, which contained both cored plaques and diffuse plaques, compared to the caudate, which contained only diffuse plaques. Three-dimensional analysis of individual plaques labeled with either ligand showed that total fluorescence output of a single cored plaque was equivalent to total fluorescence output of approximately three diffuse plaques of similar volume. Our results indicate that [18F]flutemetamol and [11C]PiB PET signal is influenced by both diffuse plaques and cored plaques, and therefore is likely a function of plaque size and density of Aβ fibrils in plaques. Brain areas with large volumes/frequencies of diffuse plaques could yield [18F]flutemetamol and [11C]PiB PET retention levels comparable to brain regions with a lower volume/frequency of cored plaques.

scholarly journals Entorhinal cortex tau, amyloid-β, cortical thickness and memory performance in non-demented subjects

Brain ◽  
2019 ◽  
Vol 142 (4) ◽  
pp. 1148-1160 ◽  
Author(s):  
David S Knopman ◽  
Emily S Lundt ◽  
Terry M Therneau ◽  
Prashanthi Vemuri ◽  
Val J Lowe ◽  
...  
Keyword(s):  
Entorhinal Cortex ◽  
Cortical Thickness ◽  
Memory Performance ◽  
Verbal Learning ◽  
Amyloid Β ◽  
Gradient Boosting ◽  
Amyloid Pet ◽  
Delayed Recall ◽  
Age Related ◽  
Z Scores

AbstractAs more biomarkers for Alzheimer’s disease and age-related brain conditions become available, more sophisticated analytic approaches are needed to take full advantage of the information they convey. Most work has been done using categorical approaches but the joint relationships of tau PET, amyloid PET and cortical thickness in their continuous distributions to cognition have been under-explored. We evaluated non-demented subjects over age 50 years in the Mayo Clinic Study of Aging, 2037 of whom had undergone 3 T MRI scan, 985 amyloid PET scan with 11C-Pittsburgh compound B (PIB) and MRI, and 577 PIB-PET, 18F-AV1451 flortaucipir PET and MRI. Participants received a nine-test cognitive battery. Three test scores (logical memory delayed recall, visual reproduction delayed recall and auditory verbal learning test delayed recall) were used to generate a memory composite z-score. We used Gradient Boosting Machine models to analyse the relationship between regional cortical thickness, flortaucipir PET signal, PIB-PET signal and memory z-scores. Age, education, sex and number of test exposures were included in the model as covariates. In this population-based study of non-demented subjects, most of the associations between biomarkers and memory z-scores accrued after 70 years of age. Entorhinal cortex exhibited the strongest associations between biomarkers and memory z-scores. Other temporal regions showed similar but attenuated associations, and non-temporal regions had negligible associations between memory z-scores and biomarkers. Entorhinal flortaucipir PET signal, PIB-PET signal and entorhinal cortical thickness were independently and additively associated with declining memory z-scores. In contrast to global PIB-PET signal where only very high amyloid-β levels were associated low memory z-scores, entorhinal flortaucipir PET signal just above background levels was associated with low memory z-scores. The lowest memory z-scores occurred with the confluence of elevated entorhinal flortaucipir PET signal and lower entorhinal cortical thickness.

Unravelling the Association Between Amyloid-PET and Cerebrospinal Fluid Biomarkers in the Alzheimer’s Disease Spectrum: Who Really Deserves an A+?

2021 ◽  
pp. 1-12
Author(s):  
Luca Sacchi ◽  
Tiziana Carandini ◽  
Giorgio Giulio Fumagalli ◽  
Anna Margherita Pietroboni ◽  
Valeria Elisa Contarino ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Amyloid Β ◽  
Standardized Uptake Value ◽  
Csf Biomarkers ◽  
Amyloid Pet ◽  
Linear Regression Models ◽  
Csf Analysis ◽  
Disease Spectrum

Background: Association between cerebrospinal fluid (CSF)-amyloid-β (Aβ)42 and amyloid-PET measures is inconstant across the Alzheimer’s disease (AD) spectrum. However, they are considered interchangeable, along with Aβ 42/40 ratio, for defining ‘Alzheimer’s Disease pathologic change’ (A+). Objective: Herein, we further characterized the association between amyloid-PET and CSF biomarkers and tested their agreement in a cohort of AD spectrum patients. Methods: We include ed 23 patients who underwent amyloid-PET, MRI, and CSF analysis showing reduced levels of Aβ 42 within a 365-days interval. Thresholds used for dichotomization were: Aβ 42 <  640 pg/mL (Aβ 42+); pTau >  61 pg/mL (pTau+); and Aβ 42/40 <  0.069 (ADratio+). Amyloid-PET scans were visually assessed and processed by four pipelines (SPMCL, SPMAAL, FSGM, FSWC). Results: Different pipelines gave highly inter-correlated standardized uptake value ratios (SUVRs) (rho = 0.93–0.99). The most significant findings were: pTau positive correlation with SPMCL SUVR (rho = 0.56, p = 0.0063) and Aβ 42/40 negative correlation with SPMCL and SPMAAL SUVRs (rho = –0.56, p = 0.0058; rho = –0.52, p = 0.0117 respectively). No correlations between CSF-Aβ 42 and global SUVRs were observed. In subregion analysis, both pTau and Aβ 42/40 values significantly correlated with cingulate SUVRs from any pipeline (R2 = 0.55–0.59, p <  0.0083), with the strongest associations observed for the posterior/isthmus cingulate areas. However, only associations observed for Aβ 42/40 ratio were still significant in linear regression models. Moreover, combining pTau with Aβ 42 or using Aβ 42/40, instead of Aβ 42 alone, increased concordance with amyloid-PET status from 74% to 91% based on visual reads and from 78% to 96% based on Centiloids. Conclusion: We confirmed that, in the AD spectrum, amyloid-PET measures show a stronger association and a better agreement with CSF-Aβ 42/40 and secondarily pTau rather than Aβ 42 levels.

IC-P-005: Does Clinical Use of Amyloid-Pet Affect Physicians’ Beliefs on The Pathogenetic Role of Amyloid-β and The Clinical Usage of Amyloid-Pet?

2016 ◽  
Vol 12 ◽  
pp. P15-P16
Author(s):  
Daniele Altomare ◽  
Clarissa Ferrari ◽  
Cristina Festari ◽  
Cristina Muscio ◽  
Orazio Zanetti ◽  
...  
Keyword(s):  
Amyloid Β ◽  
Amyloid Pet ◽  
Clinical Use ◽  
Pathogenetic Role

scholarly journals Amyloid-β Processing in Aged S100B Transgenic Mice Is Sex Dependent

2021 ◽  
Vol 22 (19) ◽  
pp. 10823
Author(s):  
Krista Minéia Wartchow ◽  
Leticia Rodrigues ◽  
Izabela Swierzy ◽  
Michael Buchfelder ◽  
Diogo Onofre de Souza ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Calcium Binding ◽  
Behavioral Responses ◽  
Amyloid Β ◽  
Brain Regions ◽  
Wild Type ◽  
One Year ◽  
Protein S100b

(1) Background: Calcium-binding protein S100B is involved in neuroregeneration but has also been associated with neurodegeneration. These contrasting effects may result from concentration or duration of exposure. We investigated the effect of long-term increased S100B levels on amyloid-β processing in one-year-old transgenic (tg) mice with 12 copies of the murine S100B gene with specific consideration of sex and specific brain regions. (2) Methods: S100B and amyloid-β 42 (Aβ42) were quantified in serum, cerebrospinal fluid (CSF), adipose tissue, and different brain regions by ELISA in wild-type (wt) and S100Btg mice (each n = 7 per group). Thioflavin T (ThT) and Aβ immunostaining were performed for visualization of Aβ deposition. (3) Results: S100B in serum, CSF, and brain was significantly increased in S100Btg mice of both sexes. Aβ42 was significantly increased in the hippocampus of male S100Btg mice (p = 0.0075), and the frontal cortex of female S100Btg mice (p = 0.0262). ThT and Aβ immunostaining demonstrated Aβ deposition in different brain regions in S100Btg mice of both sexes and female wt. (4) Conclusion: Our data validate this experimental model for studying the role of S100B in neurodegeneration and indicate that Aβ processing is sex-dependent and brain region-specific, which deserves further investigation of signaling pathways and behavioral responses.

Preliminary normative data for 12 categories using semantic verbal fluency: The role of animacy

2021 ◽  
pp. 1-6
Author(s):  
Fatima Jebahi ◽  
Rawya Abou Jaoude ◽  
Hadi Daaboul ◽  
Rhea El Achkar ◽  
Molly M. Jacobs
Keyword(s):  
Verbal Fluency ◽  
Normative Data ◽  
Semantic Verbal Fluency

scholarly journals The Role of Moderating Variables on BOLD fMRI Response During Semantic Verbal Fluency and Finger Tapping in Active and Educated Healthy Seniors

2020 ◽  
Vol 14 ◽  
Author(s):  
Claudia Rodríguez-Aranda ◽  
Susana A. Castro-Chavira ◽  
Ragna Espenes ◽  
Fernando A. Barrios ◽  
Knut Waterloo ◽  
...  
Keyword(s):  
Verbal Fluency ◽  
Finger Tapping ◽  
Bold Fmri ◽  
Moderating Variables ◽  
Semantic Verbal Fluency ◽  
Fmri Response

scholarly journals Improved amyloid burden quantification with nonspecific estimates using deep learning

2021 ◽  
Author(s):  
Haohui Liu ◽  
Ying-Hwey Nai ◽  
Francis Saridin ◽  
Tomotaka Tanaka ◽  
Jim O’ Doherty ◽  
...  
Keyword(s):  
Deep Learning ◽  
Test Scores ◽  
Amyloid Β ◽  
Standardized Uptake Value ◽  
Functional Test ◽  
Amyloid Pet ◽  
Generative Adversarial Network ◽  
Convolutional Networks ◽  
Adversarial Network ◽  
Amyloid Load

Abstract Purpose Standardized uptake value ratio (SUVr) used to quantify amyloid-β burden from amyloid-PET scans can be biased by variations in the tracer’s nonspecific (NS) binding caused by the presence of cerebrovascular disease (CeVD). In this work, we propose a novel amyloid-PET quantification approach that harnesses the intermodal image translation capability of convolutional networks to remove this undesirable source of variability. Methods Paired MR and PET images exhibiting very low specific uptake were selected from a Singaporean amyloid-PET study involving 172 participants with different severities of CeVD. Two convolutional neural networks (CNN), ScaleNet and HighRes3DNet, and one conditional generative adversarial network (cGAN) were trained to map structural MR to NS PET images. NS estimates generated for all subjects using the most promising network were then subtracted from SUVr images to determine specific amyloid load only (SAβL). Associations of SAβL with various cognitive and functional test scores were then computed and compared to results using conventional SUVr. Results Multimodal ScaleNet outperformed other networks in predicting the NS content in cortical gray matter with a mean relative error below 2%. Compared to SUVr, SAβL showed increased association with cognitive and functional test scores by up to 67%. Conclusion Removing the undesirable NS uptake from the amyloid load measurement is possible using deep learning and substantially improves its accuracy. This novel analysis approach opens a new window of opportunity for improved data modeling in Alzheimer’s disease and for other neurodegenerative diseases that utilize PET imaging.

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